During the current reporting period we focused on the role of HLA-B*51:01 in Behcet's disease (BD) susceptibility. The prevalence of BD in the Turkish population is one of the highest in the world, estimated as 4 affected per 1000. Of note, the prevalence of HLA-B*51:01, the strongest identified BD risk factor, in Turkish healthy controls is estimated as 26.5 percent, also one of the highest in the world, and the prevalence of HLA-B*51:01 is estimated as 55.6% among Turkish BD patients. It has been proposed that the high frequency of HLA-B*51:01 in this population is the result of a selective advantage conferred to carriers of this HLA allele in response to some life-threatening infection. If recent positive selection occurred, haplotypes bearing the HLA-B*51:01 allele should display unusually long linkage disequilibrium blocks for their frequency, because selection would cause a rapid rise in allele frequency over a short enough time that recombination would not substantially break down the selected haplotype. We looked for this genetic imprint of natural selection on HLA-B*51:01 carrier chromosomes from the Turkish population. Genome-wide single nucleotide polymorphism (SNP) genotypes from 1,779 healthy Turkish subjects were obtained from our previous studies. HLA alleles and MHC region SNP genotypes were imputed with the SNP2HLA application. Haplotypes were derived from genotypes with Eagle software. Extended haplotype homozygosity (EHH) and frequency normalized iHS statistic values were computed for each marker in the combined marker set with the Selscan application. The chromosome 6 region flanking HLA-B*51 exhibited extended haplotype homozygosity compared with other HLA-B alleles in the Turkish healthy control population. Of all the HLA-B alleles, HLA-B*51:01 had the strongest evidence for recent positive selection with a frequency normalized iHS statistic = 3.87 (values greater than 2.00 are suggestive of recent positive selection). These data raise the possibility that a microbial pathogen selected for this high HLA-B*51:01 frequency, which may influence reactivity to the same or cross-reactive antigens in the pathogenesis of BD.